The novel chimeric antigen receptor (CAR) T cell therapy, CT053, achieved a 100% overall response rate (ORR) for the treatment of relapsed/refractory multiple myeloma (RRMM), though toxicity was common, according to data presented at the American Society of Hematology 2020 virtual annual conference (abstract #133).
CT053 is a second-generation CAR T that incorporates a fully human B-cell maturation antigen (BCMA)-specific single-chain fragment variant. In a phase I study, CT053 induced responses in 87.5% of patients with RRMM, including 79.2% achieving a complete response (CR), for a median duration of 21.8 months.
The phase Ib LUMMICAR-2 study enrolled 20 patients with RRMM whose disease persisted after ≥3 prior lines of therapy. Participants received 500 mg/m2 cyclophosphamide for two days and 25 mg/m2 fludarabine daily three days. Following lymphodepletion, a single infusion of CT053 was administered at the 1.5-3.0×108 CAR+ T-cell target dose. At data cutoff, 14 patients received infusion and 10 were evaluated after a median 4.5 months. Primary endpoints were safety and tolerability, and identification of recommended dosing for phase II.
An ORR of 100% was achieved, with two stringent CRs, two CRs, one very good partial response, and five partial responses. Eleven of twelve patients with evaluable bone marrow samples were minimal-residual disease (MRD)-negative. All subjects showed declines in serum free light chains and soluble BCMA (sBCMA) levels at one month, with continued sBCMA depletion. Cytokine levels increased post-infusion and correlated with the onset of cytokine release syndrome (CRS) symptoms.
Toxicity was common, with twelve subjects (86%) experiencing grade 1 or 2 CRS, and one subject experiencing grade 2 neurotoxicity. CRS events occurred a median two days post-infusion with a median duration of four days. No ≥ grade 3 CRS or neurotoxicity was observed. All subjects experienced ≥ grade 3 neutropenia and leukopenia, and 36% had ≥ grade 3 thrombocytopenia.
“Collectively, these results demonstrate that CT053 at a target dose of 1.5-3.0×108 CAR+ T cells delivers early and deep responses, including MRD negativity, with an acceptable safety profile in subjects with heavily pretreated relapsed or refractory MM. The promising results from the ongoing LUMMICAR-2 study are consistent with the previous phase I studies and support the launch of a pivotal phase II LUMMICAR-2 study,” the researchers concluded.
Results from Lummicar-2: A Phase 1b/2 Study of Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT053) in Patients with Relapsed and/or Refractory Multiple Myeloma
– What is CT053
– Trial Design
– Inclusion criteria @myelomaMD #ASH20 #IMFASH20 #MMSM pic.twitter.com/HIxafnQAJJ
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— Multiple Myeloma RF (@theMMRF) December 5, 2020